PROJECT SUMMARY Jie Fan, M.D., M.Sc. has been working in the VA Pittsburgh Healthcare System (VAPHS) since 2003, and is a Director of the Multidisciplinary Surgical Research Program, a Vice Chair of the Institutional Biosafety Committee in VAPHS, and a tenured Full Professor of the Department of Surgery at the University of Pittsburgh. He is a Principal Investigator working on the cellular and molecular mechanisms of sepsis, post-trauma systemic inflammatory response syndrome (SIRS) and acute lung injury (ALI), an important but exceptionally difficult area. His laboratory has been funded by two VA merit review grants and four NIH research grants (R01, P50, and R56). The burden of trauma-related diseases is considerable. Following exsanguination and/or brain injury that commonly result in early phase death, more than 60% of surviving patients later die of causes related to the development of SIRS, sepsis, and ALI. This patient population is well suited for prophylactic interventions aimed at preventing these occurrences because of the time lag before the onset of organ inflammation and failure. Nonetheless, few specific targets have been identified that predispose to SIRS and ALI. The long term goal of Dr. Fan?s studies is to provide a new understanding of the mechanisms of post-trauma inflammation and organ dysfunction, and therefore, to potentially provide novel targets for preventive and therapeutic interventions in post-trauma SIRS, sepsis, and ALI. The studies by Dr. Fan?s team will also provide a greater understanding of the pathogenesis of multiple human diseases in which inflammation plays a central role. ALI is one of the common endpoints of SIRS and sepsis. SIRS and sepsis are common causes of mortality following surgery, infection, spinal injury, stroke, hemorrhage, and trauma in the veteran population. And thus, Dr. Fan?s research is highly relevant to Veterans? health. Dr. Fan?s research provides critical information that can be used toward the development of therapies for veterans with post-trauma inflammation and ALI. He is a highly productive Principal Investigator with a long track record of both VA and NIH funding. He has also served in roles such as Co-Investigator, Consultant, and Collaborator on numerous other research grants. His research and collaborations have resulted in 113 peer-reviewed publications, many of them in the best scientific journals and with high impact factors, including Nature Medicine, Nature Communications, Journal of Clinical Investigation, Hepatology, Journal of Hepatology, Cell Death & Differentiation, and Journal of Immunology. Dr. Fan?s work is renowned by his peers nationally and internationally. He has been an invited speaker at numerous national and international conferences and at many research and educational institutions. He serves as a reviewer in a number of national peer-review committees, including VA, NIH, DoD, and American Institution of Biological Sciences study sections. He also serves as editor-in-chief, member of editorial board, and invited reviewer for over 50 scientific journals. He has mentored 27 VA and non-VA trainees including Ph.D. candidates, postdoctoral fellows, residents, junior surgery faculties, and visiting scholars, many of whom have now become independent scientists or physician scientists. Dr. Fan is a 2010 recipient of the Excellence in Government Award for Outstanding Contribution to Medical Sciences.